Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Carolyn Rydyznski Moderbacher; Sydney I. Ramirez; Jennifer M. Dan; Alba Grifoni; Kathryn M. Hastie; Daniela Weiskopf; Simon Belanger; Robert K. Abbott; Christina Kim; Jinyong Choi; Yu Kato; Eleanor G. Crotty; Cheryl Kim; Stephen A. Rawlings; Jose Mateus; Long Ping Victor Tse; April Frazier; Ralph Baric; Bjoern Peters; Jason Greenbaum; Erica Ollmann Saphire; Davey M. Smith; Alessandro Sette; Shane Crotty

doi:10.1016/j.cell.2020.09.038

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Carolyn Rydyznski Moderbacher, Sydney I. Ramirez, Jennifer M. Dan, Alba Grifoni, Kathryn M. Hastie, Daniela Weiskopf, Simon Belanger, Robert K. Abbott, Christina Kim, Jinyong Choi, Yu Kato, Eleanor G. Crotty, Cheryl Kim, Stephen A. Rawlings, Jose Mateus, Long Ping Victor Tse, April Frazier, Ralph Baric, Bjoern Peters, Jason GreenbaumErica Ollmann Saphire, Davey M. Smith, Alessandro Sette, Shane Crotty

Research output: Contribution to journal › Article › peer-review

Abstract

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4⁺ and CD8⁺ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4⁺ and CD8⁺ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4⁺ T cell, CD8⁺ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

Original language	English (US)
Pages (from-to)	996-1012.e19
Journal	Cell
Volume	183
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2020.09.038
State	Published - Nov 12 2020
Externally published	Yes

Keywords

CD4
CD8
CXCL10
IP-10
Spike
T cells
adaptive immunity
antibody
coronavirus
epitopes
neutralizing antibodies

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2020.09.038

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Rydyznski Moderbacher, C., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., Belanger, S., Abbott, R. K., Kim, C., Choi, J., Kato, Y., Crotty, E. G., Kim, C., Rawlings, S. A., Mateus, J., Tse, L. P. V., Frazier, A., Baric, R., Peters, B., ... Crotty, S. (2020). Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell, 183(4), 996-1012.e19. https://doi.org/10.1016/j.cell.2020.09.038

Rydyznski Moderbacher, C, Ramirez, SI, Dan, JM, Grifoni, A, Hastie, KM, Weiskopf, D, Belanger, S, Abbott, RK, Kim, C, Choi, J, Kato, Y, Crotty, EG, Kim, C, Rawlings, SA, Mateus, J, Tse, LPV, Frazier, A, Baric, R, Peters, B, Greenbaum, J, Ollmann Saphire, E, Smith, DM, Sette, A & Crotty, S 2020, 'Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity', Cell, vol. 183, no. 4, pp. 996-1012.e19. https://doi.org/10.1016/j.cell.2020.09.038

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title = "Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity",

abstract = "Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.",

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month = nov,

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doi = "10.1016/j.cell.2020.09.038",

language = "English (US)",

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AU - Rydyznski Moderbacher, Carolyn

AU - Ramirez, Sydney I.

AU - Dan, Jennifer M.

AU - Grifoni, Alba

AU - Hastie, Kathryn M.

AU - Weiskopf, Daniela

AU - Belanger, Simon

AU - Abbott, Robert K.

AU - Kim, Christina

AU - Choi, Jinyong

AU - Kato, Yu

AU - Crotty, Eleanor G.

AU - Kim, Cheryl

AU - Rawlings, Stephen A.

AU - Mateus, Jose

AU - Tse, Long Ping Victor

AU - Frazier, April

AU - Baric, Ralph

AU - Peters, Bjoern

AU - Greenbaum, Jason

AU - Ollmann Saphire, Erica

AU - Smith, Davey M.

AU - Sette, Alessandro

AU - Crotty, Shane

PY - 2020/11/12

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N2 - Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

AB - Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.

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KW - CD8

KW - CXCL10

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KW - Spike

KW - T cells

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ER -

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

Abstract

Keywords

ASJC Scopus subject areas

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